In immunogenetic and other studies, sensitive and rapid methodologies for peptide and protein structural analysis are needed. Techniques utilizing mass spectrometry are promising routes to this goal. A versatile, rapid and sensitive approach using dipeptidyl peptidases (DP) and gas chromatography-mass spectrometry (GC-MS) has been developed that can analyze picomolar quantities of peptides from the N- or C- terminus. Data handling has been enhanced and simplified by computer programs. Most recent research emphasis has been placed on the C-terminal sequencing aspect of the DP/GC-MS mathodology. A number of peptides, with both free and blocked N-terminii, such as viral and tryptic peptides, have been successfully sequenced by this means. Purification schemes for the enzymes used have also been defined. Currently, several proteins are under study using the DP/GC-MS methodology.